Dehalogenation of aromatic compounds



March 25, 1952 E. C. BRITTON El' AL DEHALOGENATION OF' AROMATIC CMPOUNDS Filed Dec. 23, 1949 INVENTORS.

BYJAMES D. HEAD ATTRNEYS Patented Mar. 25, 1952 nEHALocENATIoN or ARoMATIc COMPOUNDS Edgar C. Britton and James D. Head,'lMidland,

Mich., assignors to The Dow Chemical Company, Midland, illicit., a corporation of Dela- Ware Application December 23, 1949, Serial No. 134,839

This invention relates to the dehalogenation of aromatic compounds, and, more particularlyfto a method for dehalogenating, without reducing the carbonyl group thereof, a lcarbonyl5-halo E-hydrcxy benzene compound.

It has long been known that aromatic aldehydes and ketones are readily reduced by hydrogen in the presence of certain catalysts, e. g., nickel, platinum and palladium (c. f. Recherches sur la catalyse sous pressions rduites, Bulletin dela Socit Chimique de France, 43, fourth series, page 473 (1928) It was also known prior to our invention that halogen could be removed from aromatic halides by theaction of hydrogen in the presence of certain catalysts. However, in View of the extreme ease With which aromatic aldehydes and ketones are reduced by hydro+ gen, it is logical to expect that any set of conditions suiiicient to dehalogenate a halo-substituted aromatic aldehydeor ketone would also be suiiicient to reduce the aldehyde or ketone group.

The present invention is based upon the discovery that certain lhalo-substituted aromatic aldehydes or ketones can be dehalogenated by y the action of hydrogen in the presence of a palladium catalyst Without reduction of the aldehyde or ketone group. This dehalogenation without reduction is possible only when certain conditions are used to carry out the reaction, and only to dehalogenate aromatic aldehydes or ketones having a certain structure. The method of the invention is particularly advantageous because it can be used to produce hydroxy carbonyl compounds in which the position para to the hydroxyl group is unsubstituted. This structure is essential for the production of 3-1luorosalicylaldehyde, a material valuable for the preparation of oxygen carrying cobalt chelates (cf. J. Am. Chem. Soc. 68, 2254, (1945) In the dehalogenation according to the invention, the halo substituent that is removed is chloro or bromo, and is attached to the five position of a l-carbonyl-5-halo2-hydroxybenzene compound. The dehalogenation is accomplished by bringing an aqueous solution of the compound into contact with hydrogen in the presence of a palladium catalyst while maintaining the pl-l 'of the solution between about 3.8 and '1.5. The structure of the compounds `that-may` bede 5 Claims. (Cl. 2GB-592) halogenated according to the invention may be more clearly understood by reference to the following schematic formula:

in which X is chlorine or bromine. the structure of the material that is dehalogenated in the practice of the invention is relatively unimportant. Each nuclear substituent, if any, is attached to the 3, to the 4, or to the 6 carbon atom, and hydrogen or one unreactive substituent is attached to the carbon of the carbonyl group. It is usually preferred that any substit-l uent attached to the carbon atom of the carbonyl group be a lower alkyl radical, a phenyl radical, or an aralkyl or alkaryl radical having not more than ten carbon atoms. (Lowe1- alkyl, and lower alkoxy, as used herein, refer to radicals having not more than four carbon atoms.) It is usually preferred that any substituent on the 3, 4, or 6position of the benzene ring be fluorine, a lower alkyl or lower alkoay radical, a phenyl or phenoXy radical, or an aralkyl, alkaryl, alkaroxy or aralkoXy radical having not more than ten carbon atoms.

As hereinbefore indicated, the dehalogenation of the invention is carried out in aqueous solution. When it is desired to dehalogenate a material which is not readily water-soluble, solution is accomplished by adding enough water-soluble alcohol that substantially complete solution is achieved. The alcohol does not participate in in the reaction. Any readily available alcohol can be used; methanol and ethanol are frequently employed. t

it is believed that palladium itself is the catalyst for the dehalogenation reaction that is conducted without reduction of the carbonyl group. However, because of the high cost of powdered palladium, it is usually desirable that the palladium be supplied in the form of a coatingA on some carrier. Palladium is readily available on barium sulfate and calcium carbonate as carriers, barium sulfate being the preferred carrier because pH controlis essential in the practice of the invention, and the alkalinity of calcium oar- The rest of Y bonate is likely to affect the pH of the mixture to be dehalogenated. The amount of catalyst that is ordinarily used is from about 0.1 to about 2 per cent. (The terms per cent and parts are used herein to refer toper cent and parts by weight, unless otherwise indicated.) It is usually preferred to use from about 0.25 per cent to about 0.5 per cent of the catalyst, based on the palladium actually present.

Neither the pressure, nor the temperature at which the reaction is conducted is critical. A hydrogen atmosphere must be provided to eiect dehalogenation, but the reaction can be conducted in a hydrogen atmosphere at reduced pressure or at superatmospheric pressures. Usually it is preferred to conduct the reaction at superatmospheric pressures ranging from about 2 to about 25 pounds per square inch gauge and at approximately room temperature. It is possible to conduct the reaction at pressures higher than 25 pounds per square inch gauge, but control becomes more dicult.

Although the invention is not limited by the following theoretical explanation, it is believed that reduction of the carbonyl group is prevented in the practice of the invention by the formation of a chelate structure involving the oxygen of the carbonyl group and the OH group. The following unit is believed to represent the chelate structure in which R. may be hydrogen or a substituent attached to the carbon atom of the carbonyl group. The control of pH is essential in the practice of the invention because the stable structure (assumed to be the chelate form) exists only at a relatively low pH. For example, B-uorosalicylaldehyde exists in what is believed to be the chelate form in solutions having a pH below about 4, and o-hydroxy acetophenone exists in this form in solutions having a pH below about 7.5; the presence of a chloro or bromo substituent does not affect the pH range in which this form exists.

Regardless of Whether or not the chelate structure occurs, the starting materials used in the practice of the invention exist in a stable form in solutions having a pH within a certain range. (Stable form is used herein to refer to the form in which the carbonyl group is not reduced in the course of a dehalogenation accomplished by the action of hydrogen in the presence of a palladium catalyst.) Figs. 1, 2, and 3 of the drawings show portions of the potentiometric titration curves for three materials having the same stability-pH characteristics as starting materials used in the practice of the invention. Figs. 1, 2, and 3 also` show the pH range in which the three materials exist in the stable form by showing the pH at which the visible manifestation of the stable form appears (i. e., the pH at which the change from a yellow color to a waterclear color occurs). Fig. 1 is a plot of the pH of an aqueous solution of 3-iluorosalicylaldehyde against the number of cc. of acid added thereto in the course of a potentiometric titration. Fig. 2 is a similar plot of the pH of an aqueous solution of o-hydroxy acetophenone. Fig. 3 is a similar plot of the pH of an aqueous solution of 3-methoxysalicylaldehyda A comparison of Fig. l against Figs. 2 and 3 shows that the change to the stable form does not occur over the same pH range for the three materials; this is equally true for starting materials that are used in the practice of the invention since a chloro or bromo substituent para to the hydroxyl group does not appreciably affect the pH characteristics. However, in every instance the structural change is accompanied by a color change, the material being yellow in the unstable and water-clear in the stable form. Accordingly, a convenient procedure for use in the practice of the invention is to acidify an aqueous solution of the starting material by gradual additions of an acid until the yellow color disappears and a water-clear solution is achieved. Next, the pH of the solution in the clear condition is determined, and a buffer is added to the solution that will maintain the pH close to that at which the change occurs notwithstanding liberation of HC1 or HBr made during the dehalogenation. Sodium acetate-acetic acid mixtures ordinarily constitute convenient buffers for this use because they maintain the pH in the range required in the practice of the invention.

Relatively careful pH control is needed according to the invention. Dechlorination is not induced by the action of hydrogen in the presence of a palladium catalyst at a pH lower than about 4.5. Debromination is not induced thereby at a pH lower than about 3.8. Consequently, for dechlorination, the operable pH range for any given starting material is the range between 4.5 and the pH at which the change to the stable form occurs. Similarly, for debromination, the operable range is that between 3.8 and the pH at which the change to the stable form occurs.

The process is further illustrated by the following examples which are not to be construed as limiting the invention.

Example 1 in accordance with the invention a halogen was removed from a 1carbonyl5halo2hy droxybenzene compound according to the following procedure:

A charge of 5 pounds of 5chloro2liydroxy acetophenone, 3 grams of palladium catalyst deposited on 57 grams of charcoal carrier, 5 pounds of sodium acetate butler, to maintain a pH of 5.5 to 6.5, and 8 gallons of denatured alcohol (Formula 30) was loaded into a nickel tumbler. The mixture was subjected at room temperature to hydrogen supplied at a pressure of 30 pounds per square inch gage until consumption of hydrogen ceased. The resulting product was combined with the product of two other identical runs, and the liquid was then separated from the solids by ltration. The alcohol in the combined product was then removed by distillation. Crystals which formed during the distillation were separated and the remaining liquid was subjected to vacuum distillation to recover o-hydroxy acetophenone of high purity. Further o-hydroxy acetophenone was recovered by combining the residue from this distillation with the crystals which had been removed from the crude product, washing the resulting mixture with water until all crystals had dissolved, separating the organic phase from the aqueous phase, and releasing the pure c-hydroxy acetophenone by vacuum distillation of the organic phase. In all, there were recovered a total of 6.9 pounds of o-hydroxy acetophenone (boiling point 85 C. at mm. Hg. absolute; nD25 1.5564) and 3 pounds of -chloro-oehydroxy acetophenone. The yield of c-hydroxy acetophenone based upon the 5-chloro-o-hydroxy acetophenone actually used was 69 per cent.

Example 2 A procedure similar to that for the dechlorination of 5-chloro-o-hydroxy acetophenone described in Example 1 was employed for the dechlorination of 5chloro2hydroxy benzophenone to produce o-hydroxy benzophenone. The 5-chloro-2-hydroxy benzophenone (51 grams), ethanol (125 cc.), sodium acetate (25 grams), and palladium on a charcoal carrier (2 grams of catalyst comprising 5 per cent of palladium) were placed in a flask and subjected to a hydrogen atmosphere at a pressure of about pounds per square inch gauge and shaken until a total of 0.2 gram mol of hydrogen had been consumed. The liquid in the ask was then separated from the solids by filtration and was neutralized with sodium hydroxide. 'I'he alcohol was eliminated by a distillation, and pure o-hydroxy benzophenone grams; boiling point 145 C. to 148 C. at 5 mm. Hg) was recovered by distillation. The yield based on the 5chloro2hydroxy benzophencne used was 45 per cent.

Example 3 A procedure similar to that for the dechlorination of 5-chloro-o-hydroxy acetophenone was also used for the dechlorination of 5ch1oro2 hydroxy propiophenone to produce o-hydroxy propiophenone. The 5-chloro-2-hydroxy propiophenone (37 grams), ethanol (125 grams), sodium acetate grams), and palladium on a charcoal carrier (2 grams of a catalyst comprising 5 per cent of palladium) were placed in a ask and subjected with shaking to a hydrogen atmosphere at a pressure of about 25 pounds per square inch gauge. Pure o-hydroxy propiophenone (20 grams; boiling point 95 C. to 98 C. at 13 mm. Hg) was recovered by ltration, concentration and distillation as described in Example 2. The yield corresponded to 62 per cent based upon the 5chlorochydroxy propiophenone used.

Example 4 A procedure similar to that for the dechlori., nation of 5-chloro-o-hydroxy acetophenone was employed for the debromination of 5bromo3 iluorosalicylaldehyde 1 to produce s-luorosalicylaldehyde. The 5-bromo-3-fluorosalicylaldehyde (2.19 grams), acetic acid (25 cc.), sodium acetate (2 grams) denatured alcohol (Formula Z-B) and palladium on a charcoal carrier (1 gram of a catalyst comprising 5 per cent of palladium) were placed in a 400 cc. flask and the resulting mixture was subjected to a hydrogen atmosphere at a pressure of about 15 pounds per square inch gauge and shaken for about 15 minutes. The liquid in the ilask was then separated from the solids by filtration and was made basic with sodium hydroxide. The alcohol was eliminated by a distillation; the residue was acldied with sulfuric acid; and 3.1luorosalicylaldehyde (0.81 gram) was recovered from the acidied residue by a steam distillation. The 3-fluorosalicylaldehyde not recovered by the steam distillation was converted to a Schiffs base by adding p-toluidine (2 grams dissolved in 10 cc. of 30 per cent l5-bromc-S-iluorosallcylaldehyde may be produced by direct bromlnation of -iiuorosallcylaldehyde.

acetic acid) to the residue in the flask. The precipitation of 0.90 gram of the Schiffs base indicated a total yield of S-uorosalicylaldehyde of 97 per cent.

For purposes of comparison, but not in accordance with the invention, a procedure similar to that described in the preceding paragraph was carried out using 5-chloro-3-fluorosalicylaldehyde instead of the 5-bromo-3-iluorosalicylaldehyde. It was not found to be possible to dechlorinate the chlorofluorosalicylaldehyde without reducing the aldehyde group to produce 3-fluoro-saligenin. This result illustrates the teachings contained herein inasmuch as 3-fluorosalicylaldehyde (Fig. l) assumes its stable ccndition only at a pH lower than about 4.1 whereas dechlorination proceeds only when the pH is higher than about 4.5.

We claim:

1. A method of removing a halogen having an atomic weight from 35 to 80 from the 5-position of a 1-carbonyl-5-halo-2-hydroxy-benzene compound whose carbonyl carbon atom is attached to one member of the group consisting of hydrogen, phenyl, alkyl radicals having not more than four carbon atoms, and aralkyl and alkaryl radicals having not more than ten carbon atoms which comprises bringing an aqueous solution of the compound into contact with hydrogen in the presence of a palladium catalyst, while maintaining the pH of the Solution between about 3.8 and 7 .5.

2. A method of removing chlorine from the -position of a 1-carbonyl-5-chloro-2-hydroxybenzene compound whose carbonyl carbon atom is attached to one member of the group consisting of hydrogen, phenyl, alkyl radicals having not more than four carbon atoms, and aralkyl and alkaryl radicals having not more than ten carbon atoms which comprises bringing an aqueous solution of the compound into contact with hydrogen in the presence of a palladium catalyst, while maintaining the pH of the solution between about 4.5 and 7.5.

3. A method of removing bromine from the 5position of a l-carbonyl--bromo-2-hydroxyiluorobenzene compound whose carbonyl carbon atom is attachedto one member of the group consisting of hydrogen, phenyl, alkyl radicals having not more than four carbon atoms, and' aralkyl and alkaryl radicals having not more than ten carbon atoms which comprises bringing an aqueous solution of the compound into contact' with hydrogen in the presence of a palladium catalyst, while maintaining the pH of the solution between about 3.8 and 7.5.

4. A method as claimed in claim 2 in which the 1 carbonyl 5 chloro 2 hydroxy benzene compound is 5-chloro-2-hydroxy acetophenone.

5. A method as claimed in claim 3 in which the 1 carbonyl 5 bromo 2 hydroxy benzene compound is 5-bromc-B-uorosalicylaldehyde.

EDGAR C. BRITTON. JAMES D. HEAD.

REFERENCES CITED The following references are of record ln the le of this patent:

OTHER REFERENCES Schwenk et al.: J. Org. Chem., vol. 9, pages 1-8 (1944).

Brewater et al.: J. Am. Chem. Soc.. vol. 52, pages 4866-4872 (1930). 

1. A METHOD OF REMOVING A HALOGEN HAVING AN ATOMIC WEIGHT FROM 35 TO 80 FROM THE 5-POSITION OF A 1-CARBONYL-5-HALO-2-HYDROXY-BENZENE CONPOUND WHOSE CARBONYL CARBON ATOM IS ATTACHED TO ONE MEMBER OF THE GROUP CONSISTING OF HYDROGEN, PHENYL, ALKYL RADICALS HAVING NOT MORE THAN FOUR CARBON ATOMS, AND ARALKYL AND ALKARYL RADICALS HAVING NOT MORE THAN TEN CARBON ATOMS WHICH COMPRISES BRINGING AN AQUEOUS SOLUTION OF THE COMPOUND INTO CONTACT WITH HYDROGEN IN THE PRESENCE OF A PALLADIUM CATALYST, WHILE MAINTAINING THE PH OF THE SOLUTION BETWEEN ABOUT 3.8 AND 7.5. 